Project Summary Substance addiction is characterized by compulsive and destructive choices. Decisions regarding substance use are fundamentally decisions of uncertainty regarding the negative or positive consequences that may arise. The proposed research will identify and manipulate affective factors that may play a role in decisions under uncertainty. Bringing together insights, expertise and techniques from affective science, neuroeconomics and addiction, we will systematically explore and characterize how specific affect variables modulate discrete decision processes that may be particularly common in decisions involving substance use. Specifically, we will both assess and manipulate specific components of affect ? arousal, stress, and mood -- to characterize how they may uniquely modulate three quantifiable, independent variables that contribute to decisions under uncertainty. The significance of the proposed research lies in the premise that if we can more accurately characterize the impact of affective factors on decision-making, we can use this knowledge to develop more effective means to influence choices concerning substance use. Specific Aim 1 will examine how transient arousal to the choice options, acute stress and mood may independently influence sensitivity to risk and ambiguity. Research finds that individuals are more averse to ambiguity than risk, preferring gambles with known probabilities over gambles with unknown probabilities. Decisions regarding substance use are by their nature risky and some choices more ambiguous in that the choice outcome has unknown probabilities. The proposed research examines how arousal, mood and stress independently modulate sensitivity to risk and ambiguity. Specific Aim 2 will assess how arousal, acute and chronic stress and mood modulates assessments of uncertainty in sequential decisions, specifically whether one should persist in a current course of action, or desist and pursue alternatives. The decision of whether to persist or desist is fundamentally captured in foraging decisions. The concept of foraging comes from behavioral ecology and is used to describe how animals decide to either persist in exploiting a current, depleting food resource (or patch), or desist and search for a new, uncertain, but potentially more abundant food resource at a cost of time and effort. Importantly, the basic principles of foraging have been shown to capture a range of complex human decisions, and may extend to drug use when choosing whether to stay or persist with substance abuse behavior or desist and try an alternative course of action. Across domains, optimal foraging decisions are characterized by the marginal value theorem (MVT), which allows the assessment of how different affect variables contribute to optimal, or non-optimal choices. Specific Aim 3 outlines an exploratory investigation of how an addicted population differentially responds to decisions under uncertainty pre and post-treatment.